Of the gynecologic malignancies, ovarian cancer has the highest mortality rate. Ovarian cancer often eludes the clinician because of the lack of early symptoms and signs. Hence, ovarian cancer tends to present at a late clinical stage in >85% of patients and is often followed by the emergence and outgrowth of chemotherapy-resistant disease in these patients after conventional primary cytoreductive surgery and induction chemotherapy. The American Cancer Society reported that >23,000 women were diagnosed with ovarian cancer in the United States in 2002, and 60% of those diagnosed, ≈14,000, are projected to die of their disease. More women die from ovarian cancer than from all other gynecologic malignancies combined. However, the 5-year survival rate for patients diagnosed with early-stage disease is often >90%, but it is <20% for advanced-stage disease, underscoring the importance of early detection.
The diagnostic and prognostic tumor biomarkers in use today are not adequate in distinguishing benign from malignant ovarian neoplasia and cannot differentiate among the various histological and clinically aggressive forms of ovarian cancer. The most commonly used biomarker for clinical screening and prognosis in patients with ovarian cancer is ovarian cancer antigen 125 (CA125). Serum CA125 levels are elevated in ≈80% of patients with advanced-stage epithelial ovarian cancer but are increased in only 50-60% of patients with early-stage disease. Serum CA125 levels may be falsely elevated in women with any i.p. pathology resulting in irritation of the serosa of the peritoneum or pericardium, uterine fibroids, renal disorders, and normal menses. Moreover, serum CA125 levels do not predict the outcome of cytoreductive surgery in patients with advanced epithelial ovarian cancer.
Ciphergen Biosystems (Fremont, Calif.) has developed the ProteinChip® high-throughput protein expression technology coupled with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to facilitate protein profiling of complex biological mixtures (U.S. Pat. No. 6,881,586, issued Apr. 19, 2005). In SELDI-TOF-MS analysis, a nitrogen laser desorbs the protein/energy-absorbing molecule mixture from the array surface, enabling the detection of the proteins captured by the array. The efficacy of the SELDI-TOF-MS technology for the discovery of cancer protein markers in serum has recently been demonstrated (Rai, A., et al., Arch Pathol. Lab. Med. 126:1518-1526, 2002; Kozak K R, et al., Proc Natl Acad Sci USA. 100 (21): 12343-12348, 2003).
There remains a need for improved tools to permit the early detection and prognosis of cancer, particularly ovarian cancer. There also remains a need for targets useful in the detection and treatment of cancer.